This is an application for continuation of a large multi-center, double- blind, placebo-controlled trial, using intention-to-treat analyses, that is testing the ability of the non-heparin containing mixture of sulfated glycosaminoglycurans (heparinoid/danaparolol/Org 10172) to improve important outcome events among patients with acute ischemic stroke. This trial has been funded under grant 5-R0-1-NS-27863-02 and is being submitted in conjunction with the continuing proposal by R.F.Woolson (5- R0-l-NS-27960-01). The two proposals are intended for joint review. The primary hypothesis being tested in this trial is that Org 10172 in conjunction to conventional medical care is superior to the combination of conventional medical care and placebo in improving the likelihood of a favorable outcome at three months after stroke. Antithrombotic drugs have been used in the early management of patients with acute ischemic stroke for more than 50 years. The drugs were given to prevent recurrent embolism, progression of a thrombosis, or failure of collateral circulation. These drugs may also be an important adjunct to thrombolytic therapy. Despite their widespread use, there is still considerable controversy about their efficacy and safety. The controversy largely results from the absence of any data that support the indications or contraindications for these drugs. Heparin has been complicated by serious hemorrhagic side effects and thrombocytopenia. Low molecular weight antithrombotic drugs such as Org 10172 may be safer than conventional heparin. Org 10172 is being used to prevent venous thromboses and to treat heparin-induced thrombocytopenia. Pilot studies of Org 10172 in patients with acute ischemic stroke were promising and these data were used to develop the trial that is currently underway. This carefully designed and conducted trial was funded in January, 1990. To date, the investigators have enrolled more than 650 patients of the planned 1300 at the 26 participating centers. The trial has been successful in recruiting women and minorities as subjects in this trial. A number of publications from the trial have already appeared. These papers report our development and testing of methods to conduct the trial and some baseline data. The trial recently had its mid-study interim analysis and our NINDS Safety and Monitoring Committee authorized our continued recruitment and treatment of patients. At the time of our interim analysis more than 99% of expected data had been entered in our data system. Although we are behind in recruitment, partially as the result of prolonged regulatory and administrative delays, we can achieve our goal to complete this trial. We are requesting approval and continued funding to complete this important trial. It is unlikely that future trials, of this size and scope, will test antithrombotic therapy in acute stroke.